Abstract
High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab. To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis. A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria. Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay. Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less. A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5). This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome.
Highlights
MethodsAll UK adults fulfilling Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) inclusion criteria[26] and enrolled in BADBIR27 were invited to participate
Because the first step toward defining such parameters is to determine the association between drug levels and outcome, we investigated this using a real-world bioresource from the large multicenter cohort study BSTOP (Biomarkers of Systemic Treatment Outcomes in Psoriasis) within the UK pharmacovigilance registry BADBIR (British Association of Dermatologists Biologic and Immunomodulators Register)
Meaning This study provides evidence that measurement of early ustekinumab levels could be useful to direct treatment strategy in patients with psoriasis; adequate drug exposure early in the treatment cycle may be important in determining clinical outcome
Summary
All UK adults fulfilling BSTOP inclusion criteria[26] and enrolled in BADBIR27 were invited to participate. Venous blood samples were collected between June 2009 and December 2016 during routine clinic reviews; samples from some BSTOP patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria. This study was conducted in accordance with the 2008 Declaration of Helsinki.[28] Three studies provided samples and data: a pilot study Predicting Drug Response (approved by National Research Ethics Service Committee London–South East 2; ethics approval code EC04/031), BSTOP (approved by National Research Ethics Service Committee London–South East 2; ethics approval code 11/H0802/7), and its nested study Psoriasis Stratification to Optimise Relevant Therapy Discovery (PSORTD) (approved by National Research Ethics Service Committee London–London Bridge; ethics approval code 14/LO/1685). Written informed consent was obtained from all participants before enrollment
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